By way of example, quantitative analyses are performed in order to determine toxic or otherwise undesirable substances, such as halogen compounds. In this case, the aim is to ascertain the proportion of a particular substance—or substance class—within a sample, for example in micrograms per gram (=ppm) or nanograms per gram (=ppb).
The sample or a conversion product thereof can be temporally resolved using a chromatographic method, so that the sought substance in the eluate is in available at the outlet of the chromatographic device for analysis by mass spectrometry.
The mass spectrometer may have the usual design, namely with an inlet system, an ion source, a mass analyzer, a detector and a data system. The eluate from the chromatographic method is supplied to the inlet system of the mass spectrometer.
It is also possible to perform mass spectrometric analysis without a preceding chromatographic method. This frequently results in a greater level of uncertainty in the results. The sample or a conversion product thereof is supplied, directly to the inlet system of the mass spectrometer.
Numerous substances in an organic sample—such as pollutants, valuable nutrients or other target substances—have complex molecular structures with mass-to-charge ratios of more than 100 or more than 250, in particular. Depending on the elements contained, each substance has its own characteristic isotope pattern. It is therefore possible for the mass spectrometer to be used to detect various masses with a different respective isotope content for the same substance. In this case, the various masses of the same substance are in a relatively constant ratio with one another which is characteristic of said substance. It is therefore also possible to take the quantitative determination of a single target mass or of few target masses of the sought substance and to determine said substance quantitatively overall.
For the substances which are sought, the isotope patterns and accordingly also the various (exact) masses and the proportions thereof are known generally. The user knows what he is looking for and can therefore use the known isotope pattern to choose the masses of the sought substance which are able to be detected best.
An example of the method on which the invention is based and the methodology relating thereto are described in a document from the US environmental authority EPA (Environmental Protection Agency). The document is available on the Internet at http://www.epa.gov/region03/1613.pdf. It explains the quantitative determination of specific dioxins and furans by isotope dilution in conjunction with gas chromatography and mass spectrometry. The document and the method disclosed therein are cited as EPA 1613.
The principle of the isotope solution technique is that one or more “internal standards” (i.S.) are added to a sample before the further conditioning. These are usually isotope-marked by substitution of all C atoms for 13C isotopes. In this case, the internal standard is thereby 12 units of mass heavier than the analyte referred to as “native”. The known admixture of the internal standard with the sample can be used to determine the content of the sought “native” analyte in the sample by forming a ratio between the measured value for the “native” analyte and the measured value for the internal standard. Normally, the most toxic dioxins are added as the internal standard and directly quantified by means of comparison. In addition, further dioxins found or fragments thereof which are formed in the ion source are frequently quantified simply as a sum. If appropriate, further standards are added after the sample conditioning in order to quantify the efficiency of the sample conditioning.
The invention is not limited to the determination of the cited pollutants. In principle, it is possible to determine any target substances contained in a sample using the method according to the invention.
Besides the substance which is being sought, the sample normally contains further known or unknown substances. The masses and dwell times thereof may be close to those of the substance which is being sought. The measured values for the selected masses of the sought substance can therefore be distorted by interference with other parts of the sample.
Interference between adjacent masses is visible during mass spectrometric analysis depending on the resolution of the mass spectrometer and the peak width of the respective mass. The area below the peak of the analyzed mass is a measure of the quantity of sample containing said mass. If a peak for an adjacent mass now coincides with the peak of the selected mass of the sought substance, the result is an excessive measured value for the selected mass of the sought substance, since for the selected mass not only the ions of the sought substance but also ions of the adjacent mass are included in part. The user usually does not know beforehand whether such interference is present and how great the interference is. This applies to appliances with only one detector as well as to multicollector mass spectrometers with a magnetic sector.
In order to prevent interference and hence to confirm an expected isotope pattern, it is sufficient for many applications if the ratio of two dominant mass peaks relative to one another is determined. At the same time, the target substance is often quantified only using one of the two mass peaks. For this reason, it is usual to refer to one mass (one mass peak) as the quantification mass QM and to the other mass (the second mass peak) as the comparison mass RM. This type of nomenclature is also used subsequently if appropriate for reasons of clarity. Naturally, it is possible and in many cases also expedient for both masses QM and RM to be used for the quantification. Accordingly, the terms “quantification mass QM” and “comparison mass RM” are not intended to restrict the scope of protection of the invention.
In order to detect the interference, DE 103 51 010 A1 (corresponding to WO 2004/047143) discloses the practice of splitting an ion beam into two separate ion beams using a reflecting electrode in the direction of the mass dispersion. The separate ion beams formed in this manner are directed at two separate detectors. If the signals from the two detectors differ significantly, the ion beam (before the split) has interference ions. This method requires additional hardware, namely the reflecting electrode and an additional detector. It is also necessary for the additional electrode to be aligned extremely precisely in order to ensure clean and even splitting of the ion beam. The two detectors need to be calibrated to one another. In addition, the division of the ion beam and the division ratio are permanently present.